The objective of this project is to develop an adenoviral vector vaccine against HIV that is effective in stimulating cell-mediated immunity in animals previously immune to adenovirus The HIV vaccine will be used to protect against infection and to treat the infected. Gag, Pol, and Nef are HIV proteins that have been reported to be useful for vaccine development. Evidence indicates that a broad cell-mediated immune (CMI) response is needed to treat or prevent HIV infection. Adenovirus (Ad) vector vaccines induce CMI responses and have emerged as a leading candidate to be used as a vaccine delivery platform. First Generation Ad vaccines have proven less effective than anticipated and adverse reactions are in question. Furthermore, pre-existing Ad immunity of most humans causes decreased effectiveness. To address these issues, we have developed an advanced Ad based vector that is devoid of early genes E1, E3, and E2B. "E2B-deleted" vectors, with deletions in the polymerase and preterminal protein genes, have an expanded cloning capacity and greatly reduced expression of viral late genes as compared to First Generation Ad vectors. Reduced expression of multiple Ad viral genes is advantageous for vaccine development for reasons such as reduced antigenic competition, greater longevity of expression that provides greater immunologic stimulus and reduced adverse effects. Such advantages are important in the presence of pre-existing Ad immunity since the Ad vector needs to be stealth-like. The Company has exclusive license from the U of M for the new Ad vector system and the E.C7 cell line, which supports vector production. The proposed vaccines based on the new E2B-deleted Ad vector system will carry fused Ad-gag-pol, fused Ad-gag-pol-nef and Clade C env genes. The HIV vaccines will be tested for their potential to induce CMI as a prime and for their re-immunization (boost) potential in Ad-naive and Ad-immune mice. Upon completion of this project, we will have developed a new platform for the delivery of HIV vaccines that is effective, safe, stable, cost effective, easy to distribute and use. Our goal is to initiate non-human primate studies in the Phase II SBIR and a Phase I clinical trial using these or like vaccine product within 2 to 3 years of funding as pre-clinical data allows. [unreadable] [unreadable] [unreadable]